Site-specific substitution (Q172R) in the VP1 protein of subclinical FMDV isolates collected in Vietnam

Authors: Pauszek, Steven; ESCHBAUMER, MICHAEL - Oak Ridge Institute For Science And Education (ORISE); BRITO, BARBARA - Oak Ridge Institute For Science And Education (ORISE); FERREIRA DE CARVALHO, HELENA - Oak Ridge Institute For Science And Education (ORISE); VU, LE - Ministry Of Agriculture And Rural Development (MARD); PHUONG, NGUYEN - Ministry Of Agriculture And Rural Development (MARD); HOANG, BUI - Ministry Of Agriculture And Rural Development (MARD); THO, NGUYEN - National Center For Veterinary Diagnostics; TUNG, NGUYEN - National Center For Veterinary Diagnostics; THUY, NGUYEN - Ministry Of Agriculture And Rural Development (MARD); LONG, NGO - Ministry Of Agriculture And Rural Development (MARD); DUNG, DO - Ministry Of Agriculture And Rural Development (MARD); Rodriguez, Luis; Arzt, Jonathan

Submitted to: Virology Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/6/2016
Publication Date: 10/12/2016
Citation: Pauszek, S.J., Eschbaumer, M., Brito, B., Ferreira De Carvalho, H.C., Vu, L.T., Phuong, N.T., Hoang, B.H., Tho, N.D., Tung, N., Thuy, N.T., Long, N.T., Dung, D.H., Rodriguez, L.L., Arzt, J. 2016. Site-specific substitution (Q172R) in the VP1 protein of subclinical FMDV isolates collected in Vietnam. Virology Reports. 6:90-96.

Interpretive Summary: Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals. Outbreaks of FMD, caused by FMD virus (FMDV), have a devastating effect on the affected region or country and can result in billions of dollars in losses to a variety of affected industries. One of the biggest challenges in controlling FMD is that some infected animals may become persistently infected with FMDV without showing any signs of disease. Despite much investigation, it is still unknown what specific features of FMDV determine this persistent infection. In an attempt to address these issues, the current study analyzed 114 strains of FMDV from outbreaks between 2010 and 2014in Vietnam, where FMDV is widespread. Thirty-one of these viruses were obtained in 2012 from 13 animals that showed no signs of FMD and were considered persistently infected, while the remaining 83 were from outbreak cases from which animals were obviously sick. The most remarkable change between the outbreak and persistent viruses was a single change in the virus’s genetic material and protein which occurred in all 31 of the viruses from persistently infected animals. The change is called “Q172R” which refers to the specific alteration of the virus proteins that occurred. This work provides valuable knowledge about FMDV evolution within persistently infected animals along with specific viral mutations or “triggers” associated with establishing and/or maintaining a persistent FMDV infection in natural hosts. It also lends additional support to the possibility of persistently infected animals serving as a source of new FMD outbreaks.

Technical Abstract: Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals and the FMD virus (FMDV) has been shown to persist in some affected animals for months to years following the resolution of acute infection. Viral determinants of FMDV persistence have not been elucidated and the potential ecological role of persistent FMDV in asymptomatic carrier animals, specifically its possible role in initiating new clinical outbreaks, is undetermined. In this study we analyzed 114 FMDV VP1 sequences (including 27 not previously reported sequences) collected from naturally infected animals (pigs, cattle, buffalo) in Vietnam between 2010 and 2014. Thirty-one of these sequences were obtained from 13 animals (8 cattle, 4 buffalo, 1 unspecified) that showed no signs of clinical FMD and were considered carrier animals, while the remaining 83 sequences were from outbreak cases. Despite their relative sequence heterogeneity for a single lineage (0.0%-5.6%, average of 3.1%, compared to 0.0%-8.4%, average of 2.9% for the entire dataset) and disparate placements across the corresponding phylogenetic tree, an arginine was present at VP1 residue 172 in all 31 of the carrier-associated viruses. This Q172R substitution was not associated with host species or geographic location. Moreover, this Q172R substitution was found in 28 outbreak sequences that grouped phylogenetically with a carrier-associated virus and occurred temporally after the corresponding carrier-associated virus. Additionally, we analyzed multiple viruses from a single persistently infected animal that were collected over the course of eight months (between April and November 2012, n=5) and at multiple distinct anatomical sites (n=3, collected at necropsy). This work sheds new light on intra-host viral evolution and possible viral mutations associated with FMDV persistence in natural hosts. It lends additional support to the hypothesis that persistently infected animals may serve as a source of new outbreaks.